Diabetes is a progressive debilitating disease that causes various microvascular and macrovascular complications and morbidity. Type II diabetes mellitus that is the most common type of diabetes is characterized by an increase in insulin resistance associated with inappropriate secretion of insulin after compensatory hyperinsulinemia. Free fatty acids (FFAs) are generally known to have an influence on secretion of insulin from β cells by promoting glucose-stimulated insulin secretion (GSIS), and regulate the release of insulin when G protein-coupled receptors (GPRs) expressed in the β cells respond to a change in blood sugar levels (see Nature, 2003, vol. 422, pp. 173-176). Among these, GPR40 (also known as a fatty acid receptor 1 (FFAR1)) is a membrane-bound FFA receptor that is preferentially expressed in pancreatic islets and particularly β cells to mediate heavy- and long-chain fatty acid-induced insulin secretion. It is known that compounds regulating the expression of GPR40 may be used to exhibit an incretin effect so as to promote GSIS, and may also be combined with a wide range of anti-diabetic drugs to treat diabetes, etc. Further, it is known that the compounds regulating the expression of GPR40 may be used to treat various diseases such as impaired glucose tolerance, ketosis, acidosis, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, macular edema, hyperlipidemia, genital disorders, skin diseases, arthropathia, osteopenia, arteriosclerosis, thrombotic diseases, dyspepsia, memory and learning difficulties, depression, manic depression, schizophrenia, attention-deficit hyperactivity disorder (ADHD), visual impairments, appetite dysregulation (for example, hyperorexia), obesity, hypoglycemia, hypertension, edemas, insulin resistance, labile diabetes, lipoatrophia, insulin allergies, insulinoma, lipotoxicity, pancreatic fatigue, hyperinsulinemia, cancers (for example, breast cancer), metabolic syndromes, immune diseases (for example, immunodeficiency), inflammatory diseases (for example, enteritis, arthritis, allergies), multiple sclerosis, acute renal failure, and the like, in addition to the diabetes.
There are a large number of reported compounds that have an ability to modulate a GPR40 receptor and are useful as drugs for preventing or treating diabetes. For example, WO 2004/106276 and WO 2005/051890 disclose compounds having an ability to modulate a GPR40 receptor. In recent years, WO 2008/001931, WO 2008/130514, and WO 2012/010413 disclose compounds that have an ability to modulate a GPR40 receptor and are useful as drugs for preventing or treating diabetes.
Although efforts to search for compounds modulating a GPR40 receptor have continued as described above, novel compounds having excellent efficacy are still required.